TYRP1 – Oculocutaneous Albinism Type 3

Oculocutaneous albinism type 3 (Oculocutaneous albinism type 3) is an autosomal recessive hypopigmentation disorder caused by pathogenic variants in TYRP1. A Japanese girl with classic OCA3 features was found to harbor compound heterozygous TYRP1 variants: c.88T>C (p.Cys30Arg) and a frameshift allele, confirming autosomal recessive inheritance and establishing the first East Asian case (PMID:21996312). No additional affected relatives were reported.

Functional assays demonstrate that the p.Cys30Arg variant abolishes melanin synthesis in melanocyte cultures, and recombinant intramelanosomal domain studies reveal misfolding and loss of enzymatic activity for C30R and other OCA3-associated variants such as H215Y and D308N, supporting a loss-of-function mechanism (PMID:21996312; PMID:36412553). These concordant experimental findings, together with the single proband, constitute limited genetic evidence. Key take-home: TYRP1 loss-of-function variants cause OCA3 and should be included in diagnostic evaluations of hypopigmentation syndromes.

References

• Journal of dermatological science • 2011 • Oculocutaneous albinism type 3: a Japanese girl with novel mutations in TYRP1 gene. PMID:21996312
• Protein science : a publication of the Protein Society • 2023 • In vitro characterization of the intramelanosomal domain of human recombinant TYRP1 and its oculocutaneous albinism type 3-related mutant variants. PMID:36412553

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